Alcohol Anti-Craving Medications

On Cracking Addiction this week

The aim of anti-craving medications in alcohol use disorder is to prevent relapse or decrease cravings for alcohol. They are typically prescribed for relapse prevention once acute alcohol withdrawal is over and the best evidence favours the co-prescribing of anti-craving medications with behavioural modification therapies.

Naltrexone

Naltrexone is a mu opioid receptor antagonist which blocks the endorphin mediated pleasurable effects of alcohol which reduces the rate of heavy drinking and the craving for alcohol. Naltrexone is absorbed from the gastrointestinal tract and metabolised in the liver. The side effects include nausea, diarrhoea, fatigue and headaches. Naltrexone is contraindicated in pregnancy, when using opioid analgesia for pain, in opioid dependence and severe hepatic or renal impairment.

When opioid pain relief is required naltrexone must be discontinued 72 hours prior to opioid dosing. The Sinclair method involves taking Naltrexone one hour prior to drinking to decouple pleasurable stimuli with drinking 'pharmacological extinction'.

The dose is usually 50mg daily (though it can be commenced on 25mg daily for first few days to reduce side effects) and the duration of treatment variable but can extend from 12 weeks to 12 months.

Acamprosate

Acamprosate modulates NMDA receptor transmission and GABA-A transmission and helps decrease the highly glutamatergic states associated with alcohol withdrawal. It isabsorbed from the gastrointestinal tract over four hours and has peak concentration 5-7 hours post ingestion and achieves a steady state after 7 days of usage.

Common side effects include diarrhoea, nausea, vomiting, skin rash and reduced libido. It is contraindicated in renal failure and Child Pugh C liver cirrhosis.
The common dose is 2 tablets tds if over 60kg or 2 tablets mane, 1 midi and 1 nocte if less than 60kg.

Disulfiram
Disulfiram irreversibly inhibits aldehydye dehydrogenase which is the enzyme that converts acetaldehyde to acetate and leads to an accumulation of acetaldehyde after drinking alcohol. Acetaldeyde causes an unpleasant reaction and acts as a psychological deterrent to drinking as an 'aversive therapy'. The inhibition of enzyme activity occurs in 12 hours and lasts more than 5 days.

The symptoms that it invokes includes flushing, headache, palpitations, dyspnoea, hypotension, prostration and ECG changes. Symptom onset can start within 10 minutes, peaks at 20-30 minutes and lasts for 1-2 hours. Patients need to abstain from alcohol one days before taking medication and for one week after cessation of treatment.

Common side effects include drowsiness, tiredness, confusion, headache, neuropathies, gastric upset, garlic taste and optic neuritis. Disulfiram is contraindicated in psychosis, IHD, severe renal or hepatic disease, pregnancy, allergies to compounds in medication and cognitive issues.

Disulfiram also interacts with a lot of medications including metronidazole, isoniazid, phenytoin, benzodiazepines and anticoagulants.
The dose is 100mg daily for 1-2 weeks then 200mg daily for 6 weeks to 6 months though duration of treatment is variable and maximum dosage can be 300mg daily.

Baclofen
Baclofen is a GABA-B receptor antagonist that suppresses alcohol mediated dopamine release. It has limited hepatic metabolism and well tolerated in those with chronic liver disease. It can cause sedation, drowsiness, headache, rash and urinary difficulties. Baclofen needs to be weaned gradually to avoid withdrawal syndrome such as confusion, anxiety, seizures, delusions, hallucinations and delirium.

The dose of baclofen for alcohol use disorder is given three times per day initially at 15-30mg daily (5-10mg tds) and increased to a maximum daily dose of 150mg if required.

Topiramate
Topiramate reduces glutamatergic function and enhance GABA-A receptor activity or modulate impulsivity. Common side effects include sedation, unsteadiness, paraesthesia, headache, dizziness, depression, anxiety, cognitive impairment and glaucoma. It is contraindicated in pregnancy.
The dose starts at 25mg bd and can be up to 150mg bd.